tbuckley/cabot-search huggingface dataset:
Abstract 13321: Navigating a Device Post-Approval Study During Covid-19
Authors: Devi Nair, John Garner, Allen Ciuffo, John MacGregor, Troy Rhodes, Anand Shah, Firas Hamdan, Robert Pickett, Matthew Ostrom, Donald Hopper, Nicholas Wold, Gena Kantor, Paul Tabereaux
Journal: Circulation (2022)

Background: The conduct of clinical trials during COVID-19 created challenges to ensuring access to clinical trials, healthy clinical teams, and patients. Innovative methods such as remote patient follow-up and monitoring visits can lead to successful completion of device trials. Objective: The INGEVITY+ Active Fixation Pace/Sense Lead Study examined the safety/ efficacy of the INGEVITY+ Lead in a prospective, non-randomized, multicenter, post-approval study. Methods: Subjects met indications for a pacing device with INGEVITY+ leads implanted in the RA and RV. The primary safety endpoint was the 3-month lead-related complication-free (LRC-free) rate. The primary efficacy endpoint evaluated the 3-month pacing capture threshold with the secondary efficacy endpoint evaluating the other lead-related electrical parameters. Implanter experience was assessed. Telephone visits with LATITUDE remote transmission of lead measurement data and remote monitoring visits were allowed. Results: A total of 201 leads were evaluated in 101 subjects, 46.8% female with a mean age of 73.2 years, at 13 centers in the United States. The study took 6.8 months, with a median follow-up of 3.4 months. The 3-month follow-up was completed by 98% of subjects, of which 36% were remote. A total of 98% of monitoring visits were done remotely. The study met all primary and secondary endpoints. The LRC-free rate through 3-months was 98.5% (lower CL 95.4%). Three leads were repositioned and reimplanted; two were RA dislodgements, and one was a RA perforation and hemothorax requiring thoracentesis. The pacing capture threshold was ≤ 2V in 98.9% of subjects with a mean of 0.77 V at 0.4-ms pulse width, mean pacing impedance of 712 ohms, and a median P-wave amplitude of 4.3 mV, and median R-wave amplitude of 15.9 mV at 3-months. No helix performance issues were reported. The mean turn count for helix extension was 6.7 and retraction was 7.6. More than 85% of physicians rated the lead as ‘very good’ or higher on all aspects of lead handling. Conclusions: The INGEVITY+ Lead was found to be safe and effective with a very favorable implant experience. This study was entirely conducted successfully during COVID-19 with remote follow-up and monitoring visits, and nearly half of the subjects were females.
Abstract 13936: Increased Bone Morphogenetic Protein 10 in Pulmonary Hypertension
Authors: Aida Llucia-Valldeperas, Jessie Van Wezenbeek, Joanne Groeneveldt, rowan Smal, Gonzalo Sanchez-Duffhues, Clarissa Becher, Anton Vonk Noordegraaf, Harm J Bogaard, Marie Jose Goumans, Frances S De Man
Journal: Circulation (2022)

Introduction: Pulmonary Hypertension (PH) is characterized by increased right atrial (RA) stretch and pressure. The major genetic predisposing risk factor for PH involves mutations in the bone morphogenetic protein (BMP) receptor 2 (BMPR2), for which BMP9 and BMP10 are ligands. Although BMP9 is mostly produced by hepatocytes, BMP10 is predominantly produced by adult RA cardiomyocytes. Therefore, its role is of interest in PH despite an elusive BMP10 release mechanism. Hypothesis: Increased RA wall stress in PH may be a trigger for BMP10 secretion. Methods: We first investigated BMP10 gene and protein expressions, as well as BMP activity, in RA tissue samples from control (N=5) and PH-patients (N=4). We also quantified BMP10, BMP9, IL-6 and active TGF-β plasma levels in controls (N=16) and PH-patients (N=48) by ELISA. We studied BMP10 and BMP9 activities, using a BMP-inducible reporter assay. Last, we established correlations between BMP10 activity and PH clinical parameters. Results: BMP10 mRNA, protein and activity (pSMAD1/5/8 and ID3) were increased in RA tissue of PH-patients compared to controls (Figure1 A-E). BMP10, BMP9 and IL-6 plasma levels were also augmented (Figure1 F-H); while TGF-β plasma levels, and BMP10 and BMP9 activities between PH-patients and controls were preserved. Finally, we divided the PH cohort on median BMP10-activity (0.33 AU). Higher BMP10 activity in PH-patients was associated with diminished RA compliance, reduced right ventricular function, lower stroke volume and elevated NT-proBNP (Figure1 I). Conclusions: Although BMP10 plasma levels were increased, BMP10 activity was preserved in PH-patients, probably because of high inflammatory cytokines, such as IL-6. High BMP10 activity was associated with increased RA pressure and worse disease severity in PH-patients.
Abstract 14246: Right Atrial Dilation and Conduit Dysfunction is Associated With Significant Pulmonary Insufficiency in Tetralogy of Fallot: Assessment of a New Normative Dataset
Authors: Brendan T Haughian, Timothy M Colen, Nee Scze Khoo, David E Youssef, Luke Eckersley
Journal: Circulation (2022)

Background: Right atrial (RA) size and dysfunction predicts adverse clinical outcomes in adult Tetralogy of Fallot (TOF); however limited normative or TOF data are published in children. We aimed to develop and validate 2-dimensional echocardiography normal values for RA size and function in children, by comparison with the RA of children with TOF and to determine the RA size and functional trajectory in TOF after initial repair. Methods: We prospectively imaged 156 healthy children, 13 days to 18 years, and measured RA area at end systole (RAAs), onset of ECG p wave (RAAp) and at end diastole (RAAd), to calculate total RA emptying fraction (EF) (RAAs - RAAd / RAAs), conduit EF (RAAs - RAAp / RAAs), and active EF (RAAp - RAAd /RAAs). Z-scores were developed using BSA indexing. We analysed studies at &lt;1, 3-4 and 6-7 years of age in 22 patients with TOF with sub-analysis according to degree of pulmonic regurgitation: none to mild (G1 n=7) vs. moderate or greater (G2 n=15). Results: RA area indexed to a best-fit power of BSA was homoscedastic. Normal RA conduit EF increased, and RA active EF decreased until a BSA ~1 m 2 before stabilizing, and was best fit by a linear spline function, node at BSA 1 m 2 (Figure 1). TOF RA was dilated early after repair and normalized by 4 years in G1 but not G2. Total RA EF and conduit EF, but not active EF were persistently reduced (Table 1). Conclusion: Using new z-score formulas for indexed RA size and EF, we demonstrate persistent RA dilation and conduit dysfunction in TOF is associated with significant pulmonary regurgitation. Future work will explore the potential utility of RA size and function in prediction of right heart normalization post-pulmonary valve replacement.
Abstract 13315: Differences in Infarct Size and No-Reflow by Sex in Young Adult Rats in an Electronic Cigarette Exposure Study
Authors: Wangde Dai, Jianru Shi, Lifu Zhao, Juan Carreno, Michael T Kleinman, David Herman, Rebecca J Arechavala, Samantha Renusch, Irene Hasen, Amanda Ting, Robert A Kloner
Journal: Circulation (2022)

Purpose: We investigated the effects of chronic exposure to electronic cigarettes (e-cig) on myocardial infarct size and the size of the no-reflow zone in a rat model of both sexes. Methods and Results: Sprague Dawley rats (6 weeks old) were randomized to 4 exposure groups: (1) Purified air (n=16 male/16 female); (2) e-cig vapor with 15mg/mL nicotine (n=13 male/15 female); (3) e-cig vapor without nicotine (n=16 male/12 female); and (4) Standard nicotine-containing combustion cigarette smoke (n=16 male/16 female). All rats were exposed to inhalation exposure for 8 weeks, prior to being subjected to 30 minutes of left coronary artery occlusion followed by 3 hours of reperfusion. Two-way analysis of variance (that factors sex and treatment) demonstrated that chronic exposure to e-cig vapor (with or without nicotine) or to standard cigarettes did not alter myocardial infarct or no-reflow size compared to air. However, as shown in the figure, infarct size was significantly smaller (40.7 ± 2.7% vs 54.5 ± 2.6%; p=0.0004) and no-reflow size was smaller (18.1 ± 2.0% vs 26.8 ± 2.2%; p=0.0042) in female rats compared to male rats. Conclusions: Long-term e-cig exposure did not affect the cardiac sensitivity to ischemia/reperfusion injury in young rats. Female rats are more tolerance to ischemia/reperfusion injury than males. This sex difference phenomena was not observed in our previous study [Li et al. J Thromb Thrombolysis. 1995;2(3):221-225.] that examined the tolerance between males and females subjected to 90 mins of left coronary artery occlusion followed by 4 hours of reperfusion in 1-year-old SD rats and found the myocardial infarct size to be similar between the sexes. The different findings between the 2 studies may be due to the age difference (which implies possible hormonal effects in the younger rats) or different coronary artery occlusion and reperfusion times.
Abstract 13649: Differential Effect of Variable Autonomic Modulation Stimulation Parameters on Autonomic Function
Authors: Seabrook Whyte, Rylee Barber, Karlie Sample, Faris Amil, Kassem Farhat, Stavros Stavrakis
Journal: Circulation (2022)

Introduction: Reduced heart rate variability (HRV) is associated with increased risk of cardiovascular morbidity and mortality. Previous studies have shown that transcutaneous vagus nerve stimulation (tVNS) increases HRV and improves autonomic function, but the effect of variable stimulation parameters on autonomic function remains unclear. Hypothesis: We examined the effect of variable stimulation parameters of tVNS on autonomic function. Methods: Healthy volunteers were recruited for this study. Each participant underwent autonomic function testing consisting of HRV during deep breathing and mental arithmetic stress test (MAST), with and without tVNS. Participants were randomized to 4 groups of different stimulation parameters in a 2x2 fashion (frequency 5Hz and 20Hz; amplitude 1mA below discomfort threshold or 50% below discomfort threshold). tVNS was applied for 5 minutes for each session. HRV was analyzed in a blinded fashion using Kubios software. Results were compared with 2-way ANOVA, adjusted for multiple comparisons. Results: Thirty participants were included (mean age 39±14 years, 70% female). Stimulation amplitude was 26±13 mA and 14±7 mA in the 1mA below and 50% below discomfort threshold groups (p=0.001). There was a greater change in HRV parameters with 20Hz vs. 5Hz stimulation versus baseline during MAST (low frequency: -8.1±2.8%, vs. 1.4±1.8%, p=0.01; high frequency 8.2±3.7% vs. -1.3±1.8%, p=0.03; SD2 of Poincare plot -7.9±2.9 ms vs. 4.2±3.1 ms, p=0.005, respectively; Figure). No differences were observed between the 2 different amplitude groups. Conclusions: Stimulation frequency may influence the acute effect of autonomic modulation on autonomic function parameters. These findings have implications for autonomic modulation study design. Further studies in disease states are warranted.
Abstract 13739: Racial Disparities in Cardiac Arrest Deaths in the USA: 1999-2020
Authors: Muchi Ditah Chobufo, Ebad Rahman, Paulina Skaff, Yolande Mbome, Sean Regner, yasar sattar, sudarshan balla
Journal: Circulation (2022)

Introduction: Cardiac arrest(CA) is a strong predictor of death. Survival following CA depends on timely initiation of quality cardiopulmonary resuscitation and post CA care. Significant efforts have been made in the training of individuals at delivering CPR and improving post CA aimed at reducing mortality. To assess the impact, we set out to determine the trends in age adjusted mortality rates(AAMR, per 100,000 persons) and the average annual percentage change (AAPC, %) in the USA and by gender, race and Metro area from 1999 - 2020. Methods: Using the underlying causes of death (UCOD) database from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research(1999-2020), we extracted all deaths with CA as UCOD using ICD-10 codes I46.0, I46.1, I46.9. AAMR was assessed using segmented regression models. STATA and Joinpoint softwares were used for analysis. Results: The CA related AAMR was 4.9 during the period 1999-2020. CA related deaths steadily declined from 7.7 in 1999 to 4.4 in 2020 with a statistically significant AAPC of -2.4%(95% CI -4.2 to -0.6). Ethnic specific AAMR were 8.7, 4.9, 2.8 and 3.4 for African Americans(AA), Whites, American Indian or Alaska Native and Asian or Pacific Islander, respectively. But for AA with an AAPC of -1.8%(CI -3.5 to 0.0), all other ethnic groups witnessed statistically significant decline in AAMR. AAMR were 5.3 and 5.5 for women and men, respectively. The AAPC were -2.7%(-4.5 to -0.8) and -2.5(-3.6 to -1.3) for women and men, respectively. The AAMR were 3.5, 5.6 and 8.1 for Large, Medium and Non-Metro areas, respectively, which all showed statistically significant decline. Conclusions: There has been a statistically significant decline in CA related AAMR in the USA from 1999-2020. Though AA harbor the highest AAMR, there has been no significant change in AAMR in the past two decades. Reasons for these racial disparities need to be investigated and addressed.
Abstract 14372: Case Series: Non-Lipid Plaque Formation as the Mechanism for Ponatinib-Induced Vascular Toxicity Using Operator-Assisted Virtual Histology Optical Coherence Tomography
Authors: Moez Aziz, Efstratios Koutroumpakis, Anita M Deswal, Dominique Monlezun, Nicole Thomason, Junichi Abe, Prince Otchere, Nicolas L Palaskas, Elias Jabbour, Peter Kim, Juan Lopez-Mattei, Mehmet Cilingiroglu, Konstantinos Marmagkiolis, Marc D Feldman, Cezar Iliescu
Journal: Circulation (2022)

Introduction: The third-generation tyrosine kinase inhibitor ponatinib approved for treating chronic myeloid leukemia (CML) rendered drug resistant with a threonine-315-isoleucine (T315I) mutation is associated with increased incidence of vascular adverse events (VAEs). This case series sought to elucidate the mechanism of these VAEs. Methods: Two patients with CML and two patients with Philadelphia chromosome positive acute lymphocytic leukemia (Ph+ ALL) on at least one year of ponatinib therapy were imaged with optical coherence tomography (OCT) after presenting with angina. An additional four patients from an institutional OCT database were matched across clinical parameters (age, sex, diabetes, prior coronary artery disease (CAD) history, prior congestive heart failure (CHF) history, hypertension, and family history of CAD) to serve as controls. Plaque composition was assessed using operator-assisted virtual histology OCT (vOCT). Results: Clinical presentations included 2 cases of NSTEMI, 1 case of unstable angina, and 1 case of stable angina pectoris among the 4 ponatinib patients. Atherosclerosis was composed primarily of calcium and fibrous tissue with minimal lipid presence (0 ± 0°) compared to the matched controls. The matched controls had a mean non-zero lipid content of 48.43 ± 18.36°, ( P &lt; 0.05) (Table 1). Three of the four patients had cardiovascular risk factors. Conclusions: Ponatinib causes VAEs through non-lipid plaque formation driving a symptomatology consistent with an oxygen supply-demand mismatch. This mechanism is distinct from traditional pathways of excess lipid and plaque instability causing coronary artery disease and merits further investigation.
Abstract 14149: High-Power, Low-Duration and Fluoro-Less Atrial Fibrillation Radiofrequency Ablation
Authors: Maryam Saleem, Pooneh Nabavizadeh, Muhammad Athar, Wai Tam, Alexandru Costea
Journal: Circulation (2022)

Introduction: High power radiofrequency ablation (RFA), a novel technique, is recently being employed for pulmonary vein isolation (PVI) for atrial fibrillation (AF). This study aimed to report our center’s procedural data and preliminary results of a high power RFA technique for AF without fluoroscopic guidance. Methods: Symptomatic AF patients were consecutively enrolled in this prospective observational study and underwent PVI. Ablation index (AI) was marginally used for at least 400 on the posterior wall and 500 on the anterior wall or 15 seconds total at 50 Watt ablation power, whichever came first. Contact-force catheter and esophageal temperature was used during the procedure. Post-ablation esophageal endoscopy was utilized. PVI was performed using CARTO and the ST SF D/F curve ablation catheter in a temperature-controlled mode. Results: PVI was achieved in all (n = 36, mean age: 68±11.3 years, female: 29%, CHADsVASc: 2.8±1.5, LA volume index:60.4±17.2 mL/m2). 29(80%) patients had paroxysmal AF. For left wide antral circumferential ablation (WACA); total duration was 7.4±11.3 min, total ablation sites were 49.9±11.2, average contact force was 9.97±2.2 g and average AI was 363.9±20.5. For right WACA total duration was 6.4±2 min, total ablation sites were 45.6±15.3, average contact force was 13.0±3.5 g and average AI was 403.6±32.9. WACA technique was employed for paroxysmal AF, additional ablation lines were targeted for persistent AF. For the entire flouro-less, 50W study population, average AI was 382.2±26.6, total ablation duration was 18.1±4.7 min, total ablation sessions were 118.4±33.4 and average temperature was 38.7±1.4 degree Celsius. During in-hospital follow-up no major complications such as death, stroke, tamponade, or atrio-esophageal fistula occurred. Conclusions: 50 watts fluoro-less AF RFA is a safe and efficient procedure.
Abstract 13699: Bivalirudin versus Heparin in Patients With NSTEMI Undergoing PCI: Individual-Patient-Data Pooled Analysis of the 5 Major Randomized Trials
Authors: Behnood Bikdeli, Marco Valgimigli, David Erlinge, Adnan Kastrati, Philippe G Steg, Han Yaling, Rod Stables, Roxana Mehran, Enrico Frigoli, Stefan K James, GOLDSTEIN patrick, Yi Li, Adeel Shahzad, Stefanie Schuepke, Shmuel Chen, Ghazaleh Mehdipoor, Bjorn Redfors, Aaron Crowley, Zhipeng Zhou, Gregg Stone
Journal: Circulation (2022)

Background: Whether there are treatment tradeoffs between bivalirudin and heparin in patients with NSTEMI undergoing PCI is controversial. Study-level meta-analyses lack granularity to provide conclusive answers or assess subgroups. Methods: We performed an individual-patient-data pooled analysis from all 5 large (n &gt;1000) RCTs of bivalirudin vs heparin in NSTEMI patients undergoing PCI (MATRIX, VALIDATE-SWEDEHEART, ISAR-REACT 4, ACUITY, BRIGHT). The primary efficacy outcome was the 30-day rate of all-cause mortality. Other prespecified outcomes included 30-day serious bleeding, 1-year mortality, and 30-day and 1-year MACCE, and net adverse clinical events (NACE). Subgroup analyses were performed according to access site and post-PCI bivalirudin infusion. Results: A total of 12,155 patients with NSTEMI undergoing PCI were randomized to bivalirudin alone (n=6,040, 52.3% with a post-PCI infusion) or to heparin (n=6,115, 53.2% with planned use of a GPIIb/IIIa inhibitor). Thirty-day mortality was not significantly different between bivalirudin vs heparin (aHR: 1.21; 95% CI: 0.84-1.73). There was a lower risk of 30-day serious bleeding with bivalirudin vs heparin (aHR: 0.63; 95% CI: 0.52, 0.76). At 1-year follow-up, there was no significant difference between bivalirudin and heparin for all-cause mortality (aHR: 0.97; 95% CI: 0.79, 1.19), MACCE (aHR: 1.03; 95% CI: 0.94, 1.13) or NACE (aHR: 0.92 0.84, 1.00). There were no significant differences between bivalirudin or heparin in the rates of MI or stent thrombosis (Table). Findings were consistent irrespective of access site (femoral vs radial), and post-PCI infusion of bivalirudin. Conclusions: In patients with NSTEMI undergoing PCI, procedural anticoagulation with bivalirudin was not associated with improvements in 30-day or 1-year mortality or MACCE compared with heparin with or without GPIIb/IIIa inhibitor, although serious bleeding was reduced. Full analyses will be presented at AHA 2022.
Abstract 13294: Role of Retrospective Cardiac Computed Tomography Angiography in the Detection of Prosthetic Valve Endocarditis
Authors: Mileydis Alonso, Radhika Neicheril, Yelenis Seijo De Armas, Eduardo Perez, Jose L Navia, David Lopez
Journal: Circulation (2022)

Case presentation A 47-year-old man was readmitted for evaluation of recurrent fevers, night sweats, and weight loss over a 3 month period. He had a history of bioprosthetic aortic and mitral valve replacements for rheumatic valve disease and heart failure with reduced ejection fraction due to non-ischemic cardiomyopathy. Physical examination was remarkable for a[LMD1] grade II/VI systolic murmur. Laboratory notable for neutrophilic leukocytosis elevated C-reactive protein and erythrocyte sedimentation rate. Blood cultures demonstrated Staphylococcus epidermidis . On transthoracic echocardiogram (TTE) performed in the current admission and transesophageal echocardiogram (TEE) done 2 months prior the prosthetic valves were not clearly visualized, but there was no regurgitation, stenosis or vegetation noted. Due to a high index of suspicion for prosthetic valve endocarditis (PVE), a retrospectively gated cardiac computed tomography angiography (CCTA) of the entire cardiac cycle was performed. It revealed a 13 mm mobile vegetation attached to the ventricular side of the left coronary cusp (Figure 1). Subsequently, the patient underwent a redo aortic valve replacement. Blood cultures cleared and the patient was discharged on hospital day 16 to complete 6 weeks of Cefazolin and Rifampin. Discussion: The modified Duke criteria play an important role in the diagnosis of native valve infective endocarditis (IE) (~ 80% sensitive), but it carries a lower diagnostic yield in the detection of PVE. While TEE carries high accuracy in the diagnosis of native valve endocarditis, approximately 30% of patients with PVE and/or intra-cardiac devices have inconclusive or normal echocardiographic findings. Inability to recognize IE in a timely fashion (&lt;4 days) leads to greater embolic events. We showed how CCTA can be used to expedite the diagnosis of PVE.
Abstract 14120: Proteomics of Diabetes-Related Heart Failure: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Justin B Echouffo Tcheugui, Jingsha Chen, Chiadi E Ndumele, Mary R Rooney, Christie M Ballantyne, Eric Boerwinkle, Morgan Grams, Bing Yu, Amil M Shah, Elizabeth Selvin, Josef Coresh
Journal: Circulation (2022)

Introduction: Data on the pathophysiology of diabetes-related heart failure (HF) mainly stems for animal studies . There is a paucity of large-scale human studies on proteomic alterations that characterize diabetes-related HF. Hypothesis: Diabetes-related HF has unique proteomic markers. Method: We analyzed 4,955 plasma proteins using SomaLogic v4.0 on 10,189 ARIC Study participants (Visit 2, 1990-92, mean age: 57±7 years, 56% women, 22% Black adults, 14% with diabetes [n=1477]). We used Cox regression to assess proteins associated with diabetes-related HF, in a 2/3 discovery sample and then a 1/3 validation subset, using Bonferroni correction of P -values. Results: Over a median follow-up of 24 years, there were 2417 HF events overall (605 among individuals with diabetes). After adjustment for demographics, clinical, and metabolic and biological factors (Figure), 18 proteins were associated with HF specifically among individuals with diabetes in the discovery sample ( p&lt;10 -6 ), with 13 confirmed in the validation sample ( p&lt;0.05/18 ). The validated proteins included cartilage intermediate layer protein 2 and N-terminal pro-BNP, and collagen alpha-1(XV) chain, which are not unique to diabetes-related HF. Of the validated proteins, 11 were uniquely associated with HF among diabetic individuals, and included : myocilin, lymphocyte activation gene 3 protein, and collectin-11. The latter proteins were not associated with HF among individuals without diabetes. Conclusions: A large-scale proteomics approach identified unique proteomic markers of diabetes-related HF. Pathway analysis will shed additional light on the exact role of the novel proteins in the pathogenesis of diabetes-related HF.